Polyether antibiotics monensin

The most widely used and researched growth promotant of this type is the polyether antibiotic monensin (63). Monensin, at levels of 33 p.p.m. in feed, has been shown to increase efficiency of feed utilization in both sheep and cattle fed a variety of rations by up to 12%. Slaughter and carcass analysis data indicate that the main effect of the compound is to increase the efficiency of dietary energy retention in the carcass. Its mode of action is thought to be related to its ability to increase the molar proportion of propionate, at the expense of acetate and butyrate, produced in rumen fermentation probably by an effect on the relative microfloral populations. Theoretically this should make more energy available to the animal. 

Because the stability constant of its complex with potassium is much greater than that with sodium, valinomycin is a relatively specific potassium ionophore. In contrast, the mushroom peptide antamanide has a binding cavity of a different geometry and shows a strong preference for sodium ions.388,390 The structure of the Na+-antamanide complex is also shown in Fig. 8-22B. The Streptomyces polyether antibiotic monensin (Fig. 8-22D),389,391 a popular additive to animal feeds, is also an ionophore. However, its mode of action, which involves disruption of Golgi functions, is uncertain 392... 

Quantification of five different drugs in pigs kidney Separation of carboxylic polyether antibiotics (monensin, salinomycin, and narasin) with an amino bonded phase and 15% methanol in carbon dioxide using light-scattering detector Analysis of hydroxylated metabolites of dialkyldithio-carbamates... 

Y., Staunton, J. and Leadlay, P.F. (2003) Analysis of the biosynthetic gene cluster for the polyether antibiotic monensin in Streptomyces cinnamonensis and evidence for the role of monB and monC genes in oxidative cyclization. Molecular Microbiology. 49,1179-1190. 

Bromoetherification, the addition of the elements of Br and OR to a double bond, is a common method for constructing rings containing oxygen atoms. This reaction has been used in the synthesis of the polyether antibiotic monensin (Problem 21.40). Draw a stepwise mechanism for the following intramolecular bromoetherification reaction. 

Systematic studies on the chelation-controlled additions were carried out, varying the type of alkoxy group, the carbon nucleophile, the solvent and the temperature. It was found that a-alkoxy ketones react highly stereoselectively with Grignard reagents in THF (equation 24). Alkyllithiums were not effec-tive. -6 The generalization was made use of in the synthesis of the polyether antibiotic monensin. ... 

As a final remark on podands, we should mention one innovation. Tsukube et al. proposed [114—117 a novel general approach of chemical modification of natural podands, i.e., the polyether antibiotics monensine. 

In a program aimed at the total synthesis of polyether antibiotic monensin, Ireland et al. devised a procedure for the in situ silylation of an ester enolate with a j5-leaving group, first executed with the model substrate 165 (Scheme 32). When added to a premixed solution of LDA and TMSCl in 10% HMPA/THF at -100°C, crotyl ester 165 produced after rearrangement at room temperature, desilylation, and treatment with diazomethane, the diastereomeric Claisen products 166 a and 166 b in almost 80% combined yield [63]. The success of this three-component competition experiment depended on the relative rates of N-silylation vs. enolization and -elimination vs. 0-silylation, respectively, with all of these processes occurring on a subminute time scale at -100 C. 

Still reported that triepoxide 12 was formed diastereoselectively from tri-ene 11 (dr=20 l.l, Scheme 9.1) [57, 58], Saponification followed by acid-induced cyclization gave 13, which served as a model substrate in studies towards the synthesis of the polyether antibiotic monensin B [57]. This example thus involves the use of macrocyclic stereocontrol (see Chapter 1) in the synthesis of polyketide antibiotics. 

Kishi described an elegant example of a bromoetherification reaction for effecting acyclic stereocontrol (Scheme 9.29) [162], In this case, bromide 219 was isolated as a single isomer in 57 % yield upon treatment of diolefin 218 with NBS. The presence of an allylic stereogenic center with two substituents of considerably different steric demands (Me versus 4-(3-methylbut-l-ene)) in 218 leads to a system in which interactions play a dominant role in controlling the stereochemical outcome of the cyclization. These synthetic efforts leading to intermediate 219 culminated in the total synthesis of the polyether antibiotic monensin (220) [163]. 

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